Temporal multi-omics analysis of COVID-19 in end-stage kidney disease
Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. We performed longitudinal single-cell immune profiling of ESKD patients with COVID-19. Transcriptome, surface proteome, and immunoreceptor sequencing data were generated on 580,040 high-quality cells, derived from 187 samples from 61 patients. For a subset of individuals, we obtained samples before and during infection, allowing intra-individual comparison. Longitudinal profiling demonstrated distinct temporal gene expression trajectories in severe/critical versus mild/moderate COVID-19. We identified a population of transcriptionally distinct monocytes that emerged in peripheral blood following glucocorticoid treatment. Evaluation of clonal T cell dynamics showed that the fastest expanding clones were enriched in known SARS-CoV-2-specific sequences and shared across multiple patients. Comparison with external datasets revealed upregulation of immune cell TGF-β pathway expression in ESKD, irrespective of COVID-19 status. Our data delineate the temporal dynamics of the immune response in COVID-19 in a high-risk population.
Authors
- Zewen Kelvin Tuong (ORCID: https://orcid.org/0000-0002-6735-6808)
- Michelle Willicombe (ORCID: https://orcid.org/0000-0002-6404-0584)
- Eleanor Sandhu
- Jack Gisby (ORCID: https://orcid.org/0000-0003-0511-8123)
- David Thomas (ORCID: https://orcid.org/0000-0002-9738-2329)
- Lisa M. Dratva (ORCID: https://orcid.org/0000-0002-2873-6787)
- Marina Botto (ORCID: https://orcid.org/0000-0002-1458-3791)
- Sarah Amalia Teichmann (ORCID: https://orcid.org/0000-0002-6294-6366)
- James E. Peters (ORCID: https://orcid.org/0000-0002-9415-3440)
- Maria Prendecki (ORCID: https://orcid.org/0000-0001-7048-7457)
- Lorenz Kretschmer (ORCID: https://orcid.org/0000-0003-0987-8429)
- John R. Ferdinand (ORCID: https://orcid.org/0000-0003-0936-0128)
- Rik G.H. Lindeboom (ORCID: https://orcid.org/0000-0002-3660-504X)
- Ana Peñalver (ORCID: https://orcid.org/0000-0002-5799-6780)
- Elena Prigmore (ORCID: https://orcid.org/0000-0001-8870-0316)
- Stéphane Ballereau (ORCID: https://orcid.org/0000-0002-8479-3110)
- Emily Stephenson (ORCID: https://orcid.org/0000-0002-4244-4019)
- Nicholas Medjeral‐Thomas (ORCID: https://orcid.org/0000-0003-4593-9487)
- Muzlifah A. Haniffa (ORCID: https://orcid.org/0000-0002-3927-2084)
- Stephen P. McAdoo (ORCID: https://orcid.org/0000-0001-8260-8770)
- Norzawani B Buang (ORCID: https://orcid.org/0000-0003-4897-5379)
- Erin Macdonald-Dunlop (ORCID: https://orcid.org/0000-0001-6569-6086)
- Talat H. Malik (ORCID: https://orcid.org/0000-0002-8127-6521)
- Win Tun (ORCID: https://orcid.org/0000-0003-0991-8785)
- Menna Ruth Clatworthy (ORCID: https://orcid.org/0000-0002-3340-9828)
- Anaïs Portet (ORCID: https://orcid.org/0000-0001-7592-0432)
- Candice Clarke (ORCID: https://orcid.org/0000-0001-8576-1017)
- Matthew C. Pickering (ORCID: https://orcid.org/0000-0002-1153-0192)
- Mia Cabantaus
- Benjamin J. Stewart (ORCID: https://orcid.org/0000-0003-4522-0085)
Institutions
- Imperial College Healthcare NHS Trust (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- Wellcome Sanger Institute (GB)
- Cambridge School (PT)
- Bridge University (SS)
- NIHR Newcastle Biomedical Research Centre (GB)
- Imperial College London (GB)
- Newcastle University (GB)
Publication Details
- Journal
- Cell Genomics
- Published
- 2025-06-17
- DOI
- https://doi.org/10.1016/j.xgen.2025.100918
- Citations
- 2
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 1.61